Detachment of the neural retina from the adjacent retinal pigment epithelium (RPE) results in physical separation of the photo receptor cell layer from the apical surface of the RPE, an expansion of the interphotoreceptor space (ie the subretinal space), and a concomitant change in the biochemical composition of the interphotoreceptor matrix (IPM). It also initiates a complex series of cellular and molecular changes in both retinal and RPE cells (see Fisher and Anderson, 1994). It may impede the normal transfer of ions and metabolites, and liberate or activate endogenous regulatory factors. It triggers a progressive degeneration of photoreceptor cells, and it induces a rapid proliferative response in non-neuronal retinal cells that is highly similar to the reactive gliosis that accompanies brain injury. Prompt reapposition of the retina and RPE layers can result in the arrest and/or partial reversal of some of these abnormalities, although cellular recovery is incomplete and chronic visual deficits usually persist. There are no pharmacologic treatments that can prevent, arrest, or reduce the degenerative and proliferative changes that accompany detachment or other acquired retinal degenerations. Their eventual development, however, may be predictably linked to the identification of the molecular mechanisms responsible for maintaining normal retinal adhesion, sustaining photoreceptor cell survival, maintaining mitotic quiescence, and arresting reactive gliosis. This provides a compelling rationale to examine the functions of adhesion and regulatory molecules that are normally present in the retina, and that have the potential to influence the molecular events that accompany retinal injuries such as detachment. In this proposal, the focus is on three such molecules: the vitronectin receptor (VnR), an adhesion receptor from the integrin superfamily; and two growth factors, transforming growth factor-beta (TGF-(Beta), and basic fibroblast growth factor (bFGF), both of which are thought to regulate aspects of wound healing and scar formation in the brain. The subunit composition of the integrins expressed on the surfaces of cells bordering the IPM will be identified and characterized. The involvement of this integrin(s) and its IPM ligand(s) in retinal adhesion will be assessed using in vitro and in vivo adhesion assays. Second, the function(s) of TGF-Beta1, TGF-Beta2, TGF-Beta3 isoforms will be evaluated in the context of reactive gliosis induced by retinal detachment. Finally, the processing of bFGF by retinal cells will be compared under conditions designed to induce photoreceptor degeneration (i.e. detachment) and to elicit photoreceptor cell "rescue". In pursuing these three aims, new insights should be gained into the retina's dynamic response to injury, and into the mechanisms responsible for maintaining normal retinal adhesion.